723/726 Proof of Concept Study in Allergen Challenge Chamber in Hannover

A Randomised, Double-blind, Placebo-controlled 4-period Cross-over Study to Assess the Efficacy and Safety of Repeat Dose Intranasal GSK1004723 (1000µg), Oral GSK835726 (10mg) and Cetirizine (10mg) in the Environmental Challenge Chamber in Subjects With Seasonal Allergic Rhinitis

This is a randomised, double-blind, placebo-controlled 4-period cross-over study to assess the efficacy and safety of repeat dose intranasal GSK1004723 (1000µg), oral GSK835726 (10mg) and cetirizine (10mg) in the environmental challenge chamber in subjects with seasonal allergic rhinitis.

Study Overview

• Status: Completed
• Conditions: Rhinitis, Allergic, Seasonal
• Intervention / Treatment: Drug: GSK835726 10mg; Drug: GSK1004723 1000mcg; Drug: Cetirizine 10mg; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is healthy apart from seasonal allergic rhinitis, as determined by a physician. Can have mild asthma.
• Males or female using contraceptives
• Aged 18 - 65
• Weight 50kg+, BMI 19-32 kg/m2
• Exhibit response to Challenge Chamber and skin prick test.
• Non-smoker
• Capable of giving informed consent
• AST and ALT<2xULN; alkaline phosphatase and bilirubin <or=1.5xULN

Exclusion Criteria:

• No nasal structural abnornmality/polyposis, surgery, infection.
• any respiratory disease, other than mild asthma or seasonal allergic rhinitis
• participated in another clinical study within 30 days.
• Subject has donated a unit of blood within 1 month
• Use of prescription or non-prescription drugs, including vitamins and st john's wort within 7 days of trial.
• History of sensitivty to drug
• History of alcohol/drug abuse within 12 months.
• Positive Hepatitis B antibody test
• Positive HIV antibody test
• Risk of non-compliance with study protocol
• Pregnant or llactating females
• Perenial allergic rhinitis
• Administration of oral, injectable or dermal corticosteriods within 8 weeks, intranasal or inhaled within 3 weeks.
• Past or present disease that may affect outcome, as judge by investigator
• Specific Immunotherapy within 2 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: placebo; placebo to match actives
Active Comparator: GSK835726 (10mg); 10mg oral dose	Drug: GSK835726 10mg; GSK835726 10mg tablet
Active Comparator: GSK1004723 (1000mcg); 1000mcg nasal spray solution	Drug: GSK1004723 1000mcg; GSK1004723 1000mcg nasal spray solution
Active Comparator: Cetirizine 10mg; 10mg cetirizine as active comparator	Drug: Cetirizine 10mg; Cetirizine 10mg active comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weighted Mean TNSS (Sneeze, Itch, Rhinorrhoea and Nasal Blockage) 1-6 Hours Post Start of Allergen Challenge (2-7 Hours Post-dose) on Day 3	On the third dosing day, participants entered the ECC for a duration of 6 hours, 1 hour after receiving their third dose. Time 0 hour was considered as the time that the participant entered the ECC. Nasal blockage, itch, sneeze and rhinorrhoea was scored on a categorical scale from 0 to 3 (0: no symptoms; 1: mild symptoms; 2: moderate symptoms; 3: severe symptoms). The total TNSS ranged from 0-12 point, with low score indicates well-being and higher score indicates more severity. Individual symptoms scores was summed at each time point (0, 20, 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340 and 360 minutes). The adjusted mean is provided as least square mean.	Day 3 of each treatment period (approximately up to 63 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weighted Mean of the Individual Components of TNSS (Sneeze, Itch, Rhinorrhoea and Nasal Blockage) 1-6 Hours Post Start of Allergen Challenge (2-7 Hours Post-dose) on Day 3	On the third dosing day, participants entered the ECC for a duration of 6 hours, 1 hour after receiving their third dose. Time 0 hour was considered as the time that the participant entered the ECC. Nasal blockage, itch, sneeze and rhinorrhoea was scored on a categorical scale from 0 to 3 (0: no symptoms; 1: mild symptoms; 2: moderate symptoms; 3: severe symptoms). The total TNSS ranged from 0-12 point, with low score indicates well-being and higher score indicates more severity. Individual symptoms scores was summed to produce the TNSS at each time point (0, 20, 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340 and 360 minutes). The adjusted mean is provided as least square mean.	Day 3 of each treatment period (approximately up to 63 days)
Weighted Mean Wet Tissue Weight (as a Surrogate Marker of Nasal Secretion) 1-6 Hours Post Start of Allergen Challenge (2-7 Hours Post-dose) on Day 3	On the third dosing day, participants entered the ECC for a duration of 6 hours, 1 hour after receiving their third dose. Time 0 hour was considered as the time that the participant entered the ECC. Wet tissue weight assessments was measured as a surrogate marker of nasal secretion at 60, 120, 180, 240, 300 and 360 minutes. The adjusted mean is provided as least square mean.	Day 3 of each treatment period (approximately up to 63 days)
Weighted Mean Nasal Congestion VAS 1-6 Hours Post Start of Allergen Challenge (2-7 Hours Post-dose) on Day 3	On the third dosing day, participants entered the ECC for a duration of 6 hours, 1 hour after receiving their third dose. Time 0 hour was considered as the time that the participant entered the ECC. Nasal congestion was measured on 0-10 centimeter VAS scale (0: no symptoms and 10: the worst possible symptoms) with low score indicates well-being and higher values indicate greater congestion. It was measured at 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340 and 360 minutes. The adjusted mean is provided as least square mean.	Day 3 of each treatment period (approximately up to 63 days)
Mean Forced Expiratory Volume in 1 Second (FEV1)	On the third dosing day, participants entered the ECC for a duration of 6 hours, 1 hour after receiving their third dose. Time 0 hour was considered as the time that the participant entered the ECC. FEV1 was measured at pre-challenge, 60, 120, 180, 240, 300 and 360 minutes.	Day 3 of each treatment period (approximately up to 63 days)
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or is associated with liver injury and impaired liver function defined as: alanine aminotransferase >=3 times upper limit of normal (ULN), and total bilirubin >=2 times ULN or international normalized ratio more than 1.5.	approximately up to 63 days

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Daley-Yates P, Ambery C, Sweeney L, Watson J, Oliver A, McQuade B. The efficacy and tolerability of two novel H(1)/H(3) receptor antagonists in seasonal allergic rhinitis. Int Arch Allergy Immunol. 2012;158(1):84-98. doi: 10.1159/000329738. Epub 2011 Dec 29.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 14, 2009

Study Registration Dates

• First Submitted: August 27, 2009
• First Submitted That Met QC Criteria: September 3, 2009
• First Posted (Estimate): September 7, 2009

Study Record Updates

• Last Update Posted (Actual): August 2, 2017
• Last Update Submitted That Met QC Criteria: April 19, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Proof of concept
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Histamine H1 Antagonists, Non-Sedating; Cetirizine
• Other Study ID Numbers: 112864

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Study Protocol
   Information identifier: 112864
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 112864
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Statistical Analysis Plan
   Information identifier: 112864
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: 112864
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 112864
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 112864
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: 112864
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register